We are utilizing the Chinese hamster ovary (CHO) fibroblast and the cultured human KB carcinoma cell line to study the genetics and biochemistry of some aspects of the behavior of cultured cells. Our work has emphasized morphology and its relationship to growth control, response to cyclic AMP and transforming viruses and the role of receptors and receptor-mediated endocytosis of ligands in cell behavior. We have isolated a variety of different mutants with altered microtubules which express mutated Alpha- or Beta-tubulin subunits. These mutants are defective in spindle formation. Mutants resistant to cyclic AMP have alterations in their cAMP dependent protein kinases. These mutants have been used to demonstrate that agents such as tumor promoters and interferon which raise intracellular cAMP levels do not work through a mechanism involving cAMP dependent protein kinases. Rous sarcoma virus transformed CHO cells are also resistant to growth inhibition by cAMP, but this resistance appears to be due to stimulation of viral src kinase by cyclic AMP stimulated phosphorylation. We are establishing general procedures for the isolation of mutants unable to internalize specific ligands and have isolated human KB cell mutants resistant to conjugates of Pseudomonas exotoxin and epidermal growth factor. These mutants are analyzed genetically using the techniques of somatic cell hybridization, gene cloning and gene transfer, and biochemically by classical enzymology, immunology, affinity labelling techniques an two-dimensional electrophoresis.